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Internet Journal of Medical Update, Vol. 3, No. 1, Jan-Jun 2008
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Stem Cell: Past, Present and Future- A Review Article
Dr. Sachin Avasthi* MD, Dr. R. N. Srivastava** MS, Dr. Ajai Singh*** MS, and
Dr. Manoj Srivastava**** MS
*
PhD scholar, Department of Orthopedic Surgery, K.G.M.U., Lucknow (UP), India
**
Professor, Department of Orthopedic Surgery, K.G.M.U., Lucknow (UP), India
***
Assistant Professor, Dept of Orthopedic Surgery, K.G.M.U., Lucknow (UP), India
****
SR-III, Department of surgical Oncology, K.G.M.U., Lucknow (UP), India
(Received 06 June 2007 and accepted 12 September 2007)
ABSTRACT: Stem cells are basic cells of all multicellular organisms
having the potency to differentiate into wide range of adult cells. Self
renewal and totipotency are characteristic of stem cells. Though
totipotency is shown by very early embryonic stem cells, the adult stem
cells possess multipotency and differential plasticity which can be
exploited for future generation of therapeutic options. Fortunately, the
regulators of pleuripotency such as oct-4 & nanong protein are
discovered and possibility of in vitro regulation of pleuripotency of
stem cells is gaining strength. Genetic regulation of adult stem cells in
the form of Bmi-1, Notch, sonic hedgehog & wnt gene is also being
worked upon and future can be regulation of stem cell differentiation in
vitro, in vivo or both. It is the knowledge of regulators of stem cells
which has opened the therapeutic usage of stem cells in the form of
neuron regeneration, treatment of bone defect, drug testing, gene
therapy and cell based therapy in the form of muscle damage, spinal
cord injury, cancer therapy etc. Cell based therapies might become
commercial in coming years.
KEY WORDS: Stem Cell, Review, Clinical usage, Future prospects.
INTRODUCTION:
Stem cells are primal cells common to all
multicellular organisms that retain the ability to
renew themselves through cell division and can
be differentiated into a wide range of specialized
cell types. Modern therapeutics is having a lot of
hope from stem cell research in the field of organ
transplantation and replacement of lost tissue. By
virtue of self renewal and potency, stem cells can
form various types of tissue cells. The regulators
of stem cell growth at genomic and proteomic
level are identified and we might be able to
control stem cell in vitro. In developed countries,
stem cell transplant has become a therapeutic
option but in developing countries, it is still
under trial phase. There can be two sources of
stem cells – Autologous and Allogenic.
Autologous embryonic stem cells generated
through therapeutic cloning and highly plastic
adult stem cells from the umbilical cord blood or
bone marrow are promising candidates.
Allogenic stem cells can be derived from
marrow, peripheral blood, cord blood, family
donors or HLA typed or untyped unrelated
donors. This article focuses on types of stem
cells and stem cell regulation with enlightening
comments on clinical application and future
aspects.
(Corresponding Author: Dr. Sachin Avasthi, 255/395, Kundri Rakabganj, In front of tikona park,
Lucknow (UP), India; Email: [email protected] )
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HISTORICAL BACKGROUND:
Although the first attempts were made to fertilize
mammalian eggs outside the body in 1878,
research in human stem cell field grew out of
findings by Canadian scientists Ernest A.
McCulloch and James E. Till in the 1960s1,2.
The first use of bone marrow transplant in the
present context to stem cell transplant (SCT) was
done by Schretzenmyr in 19373 as these stem
cells are known to be present in the bone marrow
of adults.4 First animal made by in-vitro
fertilization (IVF) in 1959 was also a step
towards SCT. In late 1960s, teratocarcinomas
were determined to originate from embryonic
germ cells in mice and Embryonal Carcinoma
(EC) cells were identified as a kind of stem cell.
The first human egg was fertilized in vitro in
1968 and raised the possibility of exploitation of
totipotency of stem cells. Cultured EC cells were
explored as models of embryonic development in
mice in 1970s. In 1981, it was proved that mouse
Embryonic Stem (ES) cells are derived from the
inner cell mass of blastocysts. Mouse ES cells
were grown in vitro and ES cells injected into
mice which formed teratomas. Between 19841988 pluripotent clonal cells called Embryonal
Carcinoma (EC) cells were developed. When
exposed to retinoic acid these cells differentiated
into neuron-like cells and other cell types. A
clonal line of human embryonal carcinoma cells
was derived that yields tissues from all three
primary germ layers in 1989. They had limited
replicative and differentiative capacity. In 1994,
human blastocysts were generated and the inner
cell mass was maintained in culture. Cells like
ES cells formed in the center and retained stem
cell like morphology. In 1995-96, non-human
primate ES cells were maintained in vitro from
the inner cell mass of monkeys. These cells were
pluripotent and differentiated normally into all
three primary germ layers3.
Embryonic Stem cells (ES) cells from the inner
cell mass of normal human blastocysts were
cultured and maintained normally for many
passages in 1998. In 2000, scientists derived
human ES cells from the inner cell mass of
blastocysts. They proliferated in vitro for a long
time and form all three germ layers and
teratomas when injected into immune deficient
mice. The onset of 21st century hampered the
stem cell research due to changed US funding
rules; however the funding from The California
Institute for Regenerative Medicine supported
the research. Stem cell research became more
promising as human ES cell lines were shared
and new lines were derived, more research
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groups were focusing attention
differentiation of cells in vitro.
on
the
WHAT IS STEM CELL?
Stem cells are primal cells which are considered
to be progenitor of more than 200 cell types
present in adult body. All stem cells are
unspecialized (undifferentiated) cells that are
characteristically of the same family type
(lineage). They retain the ability to divide
throughout life and give rise to cells that can
become highly specialized and take the place of
cells that die or are lost.
The rigorous definition of a stem cell requires
that it possesses two properties: Self renewal and
Unlimited potency. Self renewal means the
ability to go through numerous cycles of cell
division while maintaining the undifferentiated
state. Unlimited potency means the capacity to
differentiate into any mature cell type. In a strict
sense, this makes stem cells either totipotent or
pleuripotent. Multipotent and unipotent are also
described to define stem cell potency. These
properties can be illustrated in vitro using
methods such as clonogenic arrays where the
progeny of cells is characterized5.
Two broad categories of stem cells exist:
embryonic stem cells derived from blastocyst and
adult stem cells which are found in adult tissue.
In a developing embryo, stem cells are able to
differentiate into all the specialized embryonic
tissue. In adults, stem cells act as a repair system
for the body replacing specialized damaged cells.
POTENCY DEFINITIONS:
Potency specifies the differential potential of the
stem cells. Totipotent stem cells are produced
from the fusion of an egg and a sperm cell. Cells
produced by the first few divisions of the
fertilized egg are also totipotent. These cells can
differentiate into embryonic and extraembryonic
cell types. Only the morula cells are totipotent
able to become all tissues including a placenta.
Pleuripotent stem cells are the descendents of
totipotent cells and can differentiate into cells
derived from 3 germ layers. Pleuripotent stem
cells originate as inner cell mass within a
blastocyst (Blastula). Blastocyst is a thin walled
hollow sphere made up of an outer layer of cells,
a fluid filled cavity and an inner cell mass
containing pleuripotent stem cells. The
blastocyst develops after cleavage and prior to
implantation, in approximately 5 days. These
stem cells become any type of tissue in the body
excluding a placenta. Multipotent stem cells can
produce only cells of a closely related family of
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cells e.g. hematopoetic stem cells differentiate
into red blood cells, white blood cells, platelets
etc. Unipotent stem cells can produce only one
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cell type but have the property of self renewal
which distinguishes them from nonstem cells.
Figure 1: Potency of stem cells
TYPES OF STEM CELLS:
Stem cells are broadly classified into two
categories: Embryonic stem cells (ESC) and
Adult stem cells (ASC).
Embryonic Stem Cells:
These cells are also known as early stem cells.
Embryonic stem cells are derived from embryos
at a developmental stage before the time of
implantation would normally occur in the uterus.
This developmental stage is the blastocyst stage
– 32 cell stage, from which these pleuripotent
cells can be isolated 6.
Pleuripotency of embryonic stem cells:
Embryonic stem cells can give rise to cells from
all three embryonic germ layers i.e. ectoderm,
mesoderm and endoderm, even after being
grown in culture for a long time. In other words
they can develop into each of more than 220 cell
types of the adult body when given the sufficient
and necessary stimulation for a specific cell type.
ES cells can be maintained in culture as
undifferentiated cell lines or induced to
differentiate into many different lineages7.
Pleuripotency distinguishes ES cells from
multipotent cells found in adults, which can only
form a limited number of different cell types.
Regulation of pleuripotency of ES cells:
Researches at Genomic institute, Singapore in
collaboration with colleagues from US, have
discovered a gene that plays a crucial role in
human embryonic stem cells. Scientists studying
on mice identified a gene that encodes a
transcripion factor, Sall4, a protein that switches
gene on and off. Such transcription factors are
crucial for the identity of the cell. Transcription
factors also regulate the development of cells
from the primitive cell stage to functional cell
making up the tissue and entire development
from the fertilized egg to grown individuals.
There are various proteins described which
regulate the pleuripotency of ES cells. Some of
these are:
Oct 4 protein: It has been used as a key
marker for ES cells and for the pleuripotent
cells of the intact embryo. Its expression
must be maintained at a critical level for ES
cells to remain undifferentiated.
Nanong protein: It is essential for
maintenance of the undifferentiated state of
the mouse cells. The expression of Nanong
decreased rapidly as mouse ES cells
differentiated and when its expression level
was maintained by a constitutive promoter,
mouse
ES
cells
could
remain
undifferentiated and proliferate in the
absence of either LIF or BMP in serum free
medium. Nanong is also expressed in human
ES cells, though at a much lower level
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compared to that of Oct4 and its function in
human ES cells was yet to be examined.
Recent studies also implicate the Wnt-βcatenin
signaling
in
maintaining
pleuripotency 8.
Adult Stem Cells:
Adult stem cells are undifferentiated cells found
through out the body that divide to replenish
dying cells and regenerate damaged tissue. They
are also known as somatic stem cells which can
be found in children as well as adults.
Properties: The rigorous definition of stem cell
require that it possesses two properties: Self
renewal- the ability to go through numerous
cycles of cell division while maintaining the
undifferentiated state and Multipotency- the
ability to generate progeny of several distinct cell
type e.g. both glial cells and neurons, opposed to
unipotency restriction to a single cell type. To
ensure self renewal, stem cell undergoes two
types of cell division: symmetric division give
rise to two identical daughter cells both endured
with stem cell properties and asymmetric
division which produces only one stem cell and a
progenitor cell with limited self renewal
potential. Progenitor can go through several
round of cell division before terminally
differentiating into a mature cell. It is believed
that molecular distinction between symmetric
and asymmetric division lies in differential
segregation of cell membrane proteins (such as
receptors) between the daughter cells.
Regulation of differentiations of Adult Stem
Cells: Adult stem cell researches have been
focused on uncovering the general molecule
mechanism that control their self renewal and
differentiation.
Bmi-1: The transcriptional repressor Bmi-1
is one of the polycamb-group proteins,
which was discovered as a common
oncogene activated in lymphoma9 and later
shown to specially regulate hemato-poietic
stem cells10. The role of Bmi-1 has also been
illustrated in neural stem cells9.
Notch: The Notch pathway has been known
to developmental biologists for decades. Its
role in control of stem cell proliferation has
now been demonstrated for several cell
types including hematopoietic, neural and
mammary stem cells11.
Sonic hedgehog and Wnt: These
developmental pathways are also strongly
implicated as stem cell regulators12.
Plasticity: A change in stem cell
differentiation from one cell types to another
is called trans differentiation, and the
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multiplicity of stem cell differentiation
options is known as developmental
plasticity13,14.
Type of Adult Stem Cells: Stem cells with broad
differentiation potential appear to exist in adult
bone marrow and, perhaps, in other tissues as
well. Stem cells located outside of the bone
marrow are generally referred to as tissue stem
cells. Such stem cells are located in sites called
niches15 (niche- a specialized cellular
environment that provides stem cells with the
support needed for self-renewal. Straddling and
Xie characterized the niche cells that govern the
production of Drosophila embryonic germline
stem cells- those cells in the ovary that are the
earliest precursors to eggs. According to the
scientists, their findings offer a potentially
valuable model to explore how stem cells are
regulated in vivo). For instance in the
gastrointestinal tract they are located at isthmus
of stomach glands and at the base of crypts of the
colon. Niches have been identified in other
tissues, such as the bulge area of hair follicles
and the limbus of cornea16,17,18.
Bone marrow stem cells: Bone marrow is the
major source of adult stem cells. There are
mainly two types of marrow stem cells:
1. Bone marrow hematopoietic stem cells:
Hematopoietic stem cells are stem cells and
the early precursor cells which give rise to
all the blood cell types that includes both the
myeloid (monocytes and macrophages,
neutrophils,
basophils,
eosinophils,
erythrocytes, megakaryocytes/platelets and
some dendritic cells) and lymphoid lineages
(T-cells, B-cells, NK cells, some dendritic
cells). Hematopoietic stem cells generate all
the blood cells and can reconstitute the bone
marrow after depletion caused by disease or
irradiation19,20.
2. Bone marrow stromal stem cells: Mammary
stem cells provide the source of cells for
growth of mammary gland during puberty
and gestation and play an important role in
carcinogenesis of breast21. A single such cell
can give rise to both luminal and
myoepithelial cell types of the gland and has
been shown to regenerate the entire organ in
mouse22. Mesenchymal stem cells are
multipotent stem cells that can differentiate
into variety of cell types in vitro or vivo
include osteoblasts, chandrocytes, myocytes,
adipocytes, neuronal cells, and described
lately, into beta pancreatic ielet cells. These
cells have been classically obtained from the
bone marrow, and mesenchymal stem cells
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can some time refer to marrow stromal cells.
While the terms mesenchymal stem cell and
stromal
cells
have
been
used
interchangeably, they are increasingly
recognized as separate entities as:
Mesenchymal stem cells can encompass
multipotent cells derived from other nonmarrow tissues, such as adult muscle side
population cells or the Wharton’s jelly
present in the umbilical card; and Stromal
cells on a highly heterogenous cells
population consist of multiple cell types
with different potential for proliferation and
differentiations. In contrast, Mesenchymal
stem cells represent a more homogenous
subpopulation of mononuclear progenitor
cells possessing stem cells features specific
cell surface markers.
Neural stem cells: The existence of stem cells in
the adult brain has been postulated following the
discovery that the process of neurogenesis, birth
of new neurons, continues into adulthood in rats.
Normally adult neurogenesis is restricted to the
subventriculare zone, which lines the lateral
ventricles of the brain, and the dentate gyrus of
the hippocampal formations. Although the
generator of new neurons in the hippocampus is
well established, the presence of true self
renewing stem cells there has been debated23.
Neural stem cells are commonly cultured in vitro
as so called neurospheres – floating
heterogenous aggregates of cells, containing a
large proportion of stem cells.
Olfactory adult stem cells: Olfactory adult stem
cells have been successfully harvested from the
human olfactory mucosa cells, the lining of nose
involved in the sense of smell5.
Adipose derived adult stem cells: These cells
have also been isolated from human fat, usually
by method of liposuction. This cell population
seems to be similar in many ways to
mesenchymal stem cells derived from bone
marrow. Human adipose derived stem cells
(ASC’s) have been shown to differentiate in the
lab into bone, cartilage, fat, muscle and might be
able to differentiate into neurons, making them a
possible source for future application in the
clinic24,25.
Multipotent adult progenitor cells: The adult
bone marrow also harbors a heterogeneous
population of stem cells, which appear to have
very broad developmental capabilities called
multipotent adult progenitor cells. It has been
proposed that multipotent adult progenitor cells
constitute a population of stem cells derived
from or closely related to embryonic stem cells26
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i.e. may be adult counterpart of embryonic stem
cells.
PRESENT SCENARIO IN STEM CELL
THERAPY3:
Following types of stem cell therapy is possible
in present scenario:
Allogenic stem cell therapy: matched or
unmatched
Syngenic stem cell transplant: Identical twin
Autologous stem cell transplant
Cord blood stem cell transplant
Nonmyeloablative stem cell transplant
However stem cell therapy has some inherent
complications such as infection, regimen
toxicity, carcinogenicity, immune deficiency and
mortality due to co-occurrence of complications.
These factors make the usage of stem cell
limited. These factors not only alarm the treating
team but also open new areas of research.
Clinical application and potential use of
embryonic and adult stem cells27: There are
many ways in which human stem cells can be
used in basic research and in clinical research.
These are:
1. Embryonic stem cells have been used to
study the specific signals and differentiation
steps required for the development of many
tissues.
2. Genetic therapy: Embryonic stem cells
benefit the gene therapy by the following
ways:
First human embryonic stem cells could
be genetically manipulated to introduce
the therapeutic gene. This gene may
either be active or awaiting later
activation, once the modified embryonic
stem cells has differentiated into the
desired cell type. Recently published
reports establish the feasibility of such
an approach28. Skin cells from an
immunodeficient mouse were used to
generate cellular therapy that partially
restored function in the mouse. This can
also be used in treating human patient
with immuno deficiency.
Embryonic stem cells may additionally
be indirectly beneficial for cellular gene
therapy. Since these cells can be
differentiated into many cell types,
including presumably tissue specific
stem cells, they may provide a constant
in vitro source of cellular material. Such
"adult" stem cells derived form
embryonic stem cells may thus be
utilized to optimize protocols for
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3.
4.
5.
6.
7.
propagation and genetic manipulation
technique29.
Drug Testing: Because embryonic stem
cells can proliferate without limit and can
contribute to any cell type, human
embryonic stem cells offer an unprecedented
access to tissue from the human body. They
will support basic research on the
differentiation and function of human tissues
and provide materials for testing that may
improve the safety and efficacy of human
drugs30,31 for example, new drugs are not
generally tested on human heart cells
because no human heart cell lines exist.
Instead researchers rely on animal models.
Because of important species specific
differences between animal and human
heart, however, drugs that are toxic to the
human heart have occasionally entered
clinical trials, sometimes resulting in death.
Human ES cells – derived heart cells may be
extremely valuable in identifying such drugs
before they are used in clinical trials, there
by accelerating the drug discovery process
and leading to safer and more effective
treatments32,33,34 .
Cell based therapies: It is perhaps the most
important potential application of human
stem cells. They generate cells and tissues
that could be used for cells based therapies.
Stem cells, directed to differentiate into
specific cell types, offer the possibility of a
renewable source of replacement cells and
tissues to treat various disease.
Brain Damage8,35,36: In the case of brain
injury although reparative process appears to
initiate, substantial recovery is rarely
observed in adults suggesting a lack of
robustness.
Recently
from
research
conducted in rats subjected to stroke
suggested that administration of drugs to
increase the stem cell division rate and
direct the survival and differentiation of
newly formed cells could be successful.
Cancer: Researcher at Harvard Medical
School caused intracranial tumor in rodents.
Then they injected human neural stem cells.
Within days the cells had migrated into the
cancerous and produced cytosine deaminase,
an enzyme that convents a non-toxic prodrug into a chemotherapeutic agent. As a
result, the injected substance was able to
reduce tumor mass by 80 percent 12,21.
Spinal cord injury: Recently extensive
study work is carried out in treating spinal
cord injury. Scientist have treated the patient
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8.
9.
of spinal cord injury by isolating adult stem
cells from umbilical cord blood and then
injected them into damaged part of the
spinal cord37.
Muscle damage: Adult stem cells are also
apparently able to repair muscle damaged
after heart attacks. Heart attacks are due to
coronary artery being blocked, staring tissue
of oxygen and nutrients. Days after the
attack is over, the cells try to remodel
themselves in order to become able to pump
harder. However, because of the decreased
blood flow this attempt is futile and results
in even more muscle cells dying.
Researchers found that injecting bone
marrow stem cells, a form of adult stem
cells, into mice which had heart attacks
induced resulted in an improvement of 33%
in the functioning of heart. The damaged
tissue had regrown by 68%14,38.
Heart damage: Several clinical trials
targeting heart disease have shown that adult
stem cell therapy is safe. However none of
these trials have proven efficacy. Recently
the use of patients own bone marrow
derived stem cells and peripheral blood
derived stem cells is becoming popular33,34.
CONTROVERSIES
IN
STEM
CELL
RESEARCH:
Stem cell research is a minefield of ethical
problems because stem cells that offer the most
potential for study must be harvested from
human embryos that are a few days old. In 1996,
the birth of Dolly the sheep -- the world’s first
successfully cloned mammal -- ignited a
firestorm of protest and concern. The most
famous controversy in stem cell research has
been Hwang’s claim of cloning a dog. Hwang's
work was able to offer an alternative to use of
actual human embryo by cloning several human
embryos, helping to eliminate the need for new
embryos. Hwang claimed he had successfully
cloned 30 human embryos, claims that have now
been shown to be lies. Unfortunately, the use and
study of embryonic stem cells are currently
clouded by ethical controversy. Adult stem cells
offer a unique alternative in that they may be
isolated, studied, or manipulated without
harming the donor. Currently, several obstacles
for use of adult stem cells as therapy exist. First,
the ability to identify most adult stem cells is
impeded by lack of stem cell markers. Second, in
vitro systems for manipulating adult stem cell
populations are often not well defined. Finally,
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our understanding of how adult stem cells are
regulated within their niche is in its infancy.
FUTURE PERSPECTIVES OF STEM CELL
RESEARCH:
Low blood supply: Now the method to
produce large numbers of Red blood cells
has been developed. In this method
precursor Red blood cells, called
hematopoietic stem cells are grown together
with stromal cells, creating an environment
that mimic the conditions of bone marrow,
the natural site of red blood cell growth.
Erythropoietin, a growth factor, is added
coaxing the stem cells to complete terminal
differentiation to red blood cells.
Further research into this technique will
have potential benefits to gene therapy&
blood transfusion.
Baldness: Hair follicles also contain stem
cells, and some researchers predict research
on these follicle. Stem cell may lead to
successes in treating baldness through "hair
multi-placation" and known as "hair
cloning" as early 2011. This treatment is
expected to work through taking stem cells
from existing follicles, multiplying them in
cultures, and implanting the new follicle
cells which have shrunk during the ageing
process, which in turn respond to these
signals by regenerating and once again
making healthy air17.
Missing teeth: The work on tooth
generation has reached to a stage that it will
be available to the general population in that
decade. In theory, stem cells taken from the
patient could be coaxed in the lab into
turning into a tooth bud which, when
implanted in the gums, will give rise to a
new tooth, which would be expected to take
two months to grow. It will fuse with jaw
bones and release chemicals that encourage
nerve and blood vessels to connect with it.
Deafness: Those have been success in
regrowing cochlear hair cells with the use of
stem cells.
Blindness and vision improvement18:
Since 2003 research have successfully
transplanted retinal stem cells into damaged
eye to restore vision. Using embryonic stem
cells, scientists become able to grow the
sheet of top potent stem cells in the
laboratory. When these sheets are
transplanted over the damaged retina, the
stem cells stimulate neural repair, eventually
restoring vision. The group led by Dr.
Sheraz Daya was able to successfully use
adult stem cells obtained from the patient, a
relative, or even a cadaver. Further rounds
of trials are ongoing.
Bone regenerations: Mesenchymal stem
cells can be pumped and cutters expanded
from animals and human and have been
shown to regenerate functional tissue when
delivered to the site of musculo-skeletal
defects
in
experimental
animals.
Mesenchymal stem cells can regenerate
bone in a clinically significant osseous
defect and may therefore provide an
alternative to autogenous bone grafts.
Diabetes Type I: In people who suffer from
type I diabetes, the cells of the pancreas that
normally produce insulin are destroyed by
the patient's own immune system. New
studies indicate that it may be possible to
direct the differentiation of human
embryonic stem cells in the cell culture to
form insulin-producing cells that eventually
could be used in transplantation therapy for
diabetics.
ETHICAL CONCERNS IN STEM CELL
RESEARCH:
In the case of embryonic stem cell research, the
end that scientists hope to achieve is the relief of
human suffering. That this is a humanitarian and
worthy end is not in dispute. The controversy is
about the means, namely, the consumption of
donated embryos. More particularly, embryonic
stem cell research and therapy would use
donated embryos that, by virtue of donor
instructions, will never enter a uterus. Is it
permissible to use those means to that end? Our
task is to decide how we should act toward an
embryo, and whether we should recognize, as we
do among adults, distinctions between embryos
of various types and in various circumstances.
We immediately encounter the question of what
beings we should classify as "persons" for
purposes of the duty not to kill persons. For one
who concludes that we are not obliged to refrain
from using embryos that will never enter a
womb, embryonic stem cell research is a case of
fostering a worthy end by using only nonpersons
as means.
CONCLUSION:
Stem cells pose a bright future for the therapeutic
world by promising treatment options for the
diseases which are considered as noncurable now
a days. However, because of significant peri and
post-transplant morbidity and mortality further
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research and trials are required to refine and
optimize conditioning regimens and modalities
of supportive care. By virtue of funding of stem
cell research, we hope to see new horizon of
therapeutics in the form of organ development
and replacement of lost tissue such as hairs,
tooth, retina and cochlear cells.
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